Villainous Acts, Part 1: How Data and Debate are Misappropriated
As I recently posited, there is no “safe,” there is no zero risk, there is only acceptable risk. And as we contemplate the removal of COVID-19 restrictions, the term “acceptable risk” should be on everyone’s mind.
Life carries risk. That’s neither good nor bad — it just is. Good decisions rest on balancing risks and benefits and finding the level of each that we are willing to live with. But for some reason, the current debate in the U.S. seems not to be risk vs. benefit but rather safe vs. unsafe. The latter is a dangerously deceptive debate which is likely to lead to polarization as well as pseudomoralistic justification and shaming. What it probably will not lead to is a considered, balanced decision.
In the interests of a considered, balanced debate, therefore, let’s examine and dispel some common misunderstandings so we can actually understand and discuss the relevant issues instead of merely taking a side and trying to “win” the argument. We'll be doing this by identifying our foes, and discussing how they're being tested, tracked, and reported.
The Villains
Definitions
A few definitions will be useful as we discuss our villains — COVID-19, SARS-CoV2 and more.
Infection
An infection is the invasion and multiplication of microorganisms — such as bacteria, viruses, and parasites — that are not normally present within the body.
It’s important to know that an infection does not necessarily mean you are sick. Various microbes — including SARS-CoV2 — may invade the body, reproduce for a while, get identified as a foreign invader by the immune system, and then be eliminated from the body before we even feel a thing.
Note that microorganisms aren’t necessarily bad: many, many of them live in healthy people who depend on them for all kinds of reasons; they make up the “microbiome” and do not cause “infections” (by definition). What’s more, the same microbe that causes an infection in one person may be a normal member of the microbiome in another person — and therefore not an infection.
Disease/ Illness
In contrast to an infection, an illness is generally defined by certain subjective symptoms (like pain), objective signs (like swelling or redness), and/or diagnostic data (like a high blood pressure or a low sodium reading).
Pneumonia, for example, is a disease. It usually comes with subjective symptoms (a cough, fatigue), objective signs (fever, altered lung sounds you can hear with a stethoscope), and diagnostic data (a high white blood cell count, an abnormal chest x-ray). Infection with the virus SARS-CoV2 can cause the disease of pneumonia, but so can infection with influenza virus, Mycoplasma pneumoniae (a type of bacteria), Mycobacterium tuberculosis (another type of bacteria), and many other microbes.
So we say that “pneumonia” is a disease which can be caused by an infection with a microbe like Mycoplasma. Pneumonia may have other causes, and Mycoplasma infection may also cause other diseases (like chronic fatigue syndrome). “Respiratory Distress,” similarly, is an disease (or illness, if you prefer) that can be caused by SARS-CoV2 infection or something else, and SARS-CoV2 may cause the illness respiratory distress or something else (like the common cold).
The point is that being infected with a virus and having a disease are not the same thing.
Virus
A virus is a type of “thing”, like an animal or a plant, that infects another organism and replicates itself inside living cells.
Viruses are a bit of a problem for scientists. Technically, they aren’t exactly living things: viruses can’t exist independently and need other cells to survive and replicate. So there’s a bit of debate about whether they really “count” as whole beings or if we should consider them to be more like a random kidney which cannot function without a body. Whatever the case, the terminology surrounding them is a bit different from the rest of life science (since they aren’t exactly “life”), and sometimes confusing.
The term “virus” describes a type of thing, analogous to the terms “animal,” “plant,” “fungus,” etc. Within the virus category, there are subtypes, such as the coronavirus subtype. Within these, there are sub-sub-types like SARS-CoV2. Each individual thing in the SARS-CoV2 category is called a “virus particle” or a more Star-Trek-sounding “virion” (my preference, naturally).
All virions in the SARS-CoV2 category are exact replicas of each other: clones. They are not like, say, cats where each individual cat is a little bit different from all the other cats in its breed. The instant a virion makes a change from its mates — even just a little bit — it has just become a new type of virus. If it is discovered by scientists, it gets a new name: usually a boring alphanumeric sequence.
How Viruses Work
But let’s take a step back and talk about how viruses work.
First, viruses can infect pretty much all types of cells that we know about — single-celled bacteria, plant cells, animal cells, human cells, etc.
A virion floats around for a bit in an organism’s tissues (for SARS CoV2 usually it’s the throat or nose), until it can find its way into a cell that is just going about its business.
Then the virion convinces the cell to stop doing its job and start making copies of the viral genes and various viral pieces.
At some point, the viral pieces get collated and packaged into individual virions.
They then burst out of the host cell (sometimes killing it) and float around for a while, looking for their own host cells to infect.
Inevitably, all this hopping in and out of cells and borrowing other cell’s stuff leads to a lot of mistakes when it comes to virus replication. “Mistakes” are mutations, which is why viruses mutate so quickly.
The basic viral strategy is simply to pass on as many copies of as many genes as possible. If some of them get mucked up, oh well. There will probably be enough of the others that it doesn’t matter. Besides, each virion does not have to put together an entire complex, fully functional organism, so it can afford to mess a lot of things up. When the messed up ones accidentally stumble into some kind of advantage over the other ones, they out-reproduce the original ones. Once the new version gets transmitted to another organism, voila! you have a new variant — a new “species,” if you will (although we can’t call them “species” because they aren’t really living things).
This is what happens every year with influenza (a type of virus). One version of the flu virus makes the rounds and gets killed off by human after human. Before it circles the globe and runs out of humans, a new variant — ie, a messed up reproduction of the original type — will emerge and start making its rounds. Meanwhile, the original version (which can’t re-infect most people who have already contacted it) will eventually run out of humans and die. At that point, not just the individual virions die but the whole species — or variant, or whatever you want to call it. It goes extinct (except for the few copies that the CDC keeps on hand just in case we need them again for some reason, whatever that may be).
Another way to say this is that when our super-hero immune systems catch on to the original virus, it needs to change its tune pretty quickly, or it will be exterminated. So viruses are under a lot of pressure to evolve or die. Through millennia of trial and error, they have devised ingenious ways to evade and disable immune mechanisms, hop from species to species, and get transmitted from individual to individual. They absolutely define sneakiness.
Virulence
How “strong” a virus is.
One of the sneakiest self-preservation mechanisms of viruses is to actually to become less virulent, or “weaker.” Viruses “want” just enough strength to get past the immune system but not so much that they kill their host organism. Killing a host quickly is a death sentence for the virus itself. Even if it just makes you really sick, you might sequester yourself from your herd, which limits the chance of the virus to get into other hosts.
One winning strategy for a virus is to make the host just a little bit sick, or maybe not even sick at all. That way, they keep walking around and spreading the virus to everyone. The all-time jackpot strategy for a virus is to integrate its genes into the host’s DNA. That way, the host will pass on the viral genes to all its cells and to its offspring, ad infinitum. Those viruses can basically chill, without all the cell hopping and re-assembling and mistake-making. About 8% of our genome is made of up of DNA from viruses that took this approach.
The point is that viruses don’t “want” to kill us. They do sometimes make us uncomfortable, as they try to get into our respiratory droplets or sweat or stool on their way to another organism. But kill us? No way. Viruses need us.
We don’t really know how virulent SARS-CoV2 is. We often measure virulence in terms of a virus’s “death rate,” the percentage of people who die out of the total number of people who are infected with the virus (whether they are actually sick or not). Unfortunately, because of the way the CSTE and CDC have chosen to collect the data, it will be a long time before we know the true death rate of SARS-CoV2. As I mentioned earlier, the CDC is not actually tracking SARS-CoV2 (or, at least, they’re not telling us about it, if they are).
Given those definitions, let’s now introduce the main players in our game.
The Players
COVID-19
Literally, “COronaVIrus Disease-19.” In other words, the disease caused by the virus named SARS-CoV2. We hear these terms used interchangeably in the popular press, but the disease and the virus are different entities. The CDC does not track the spread of the virus. It does track COVID-19, however, including “confirmed and probable cases,” as defined by the Council for State and Territorial Epidemiologists (CSTE) on April 05, 2020.
According to these standards, no confirmation of infection with the virus SARS-CoV2 is necessary to be counted as a “case.” Furthermore, the “cases” includes both sick people without any lab tests AND healthy people with positive lab tests. Also, although the title COVID-19 implies the presence of respiratory failure, this is actually not necessary to be defined as a case. Ie, anyone in the U.S. since late February who told their health care provider they had a cold could be counted as a COVID-19 “case.”
Here are some other examples that could be reported as a “confirmed or probable case” of COVID-19, if people have consulted a health care provider:
A healthy, asymptomatic 14 year old with SARS-CoV2 RNA (genetic remnants of the virus) found on a throat swab.
An active 23 year old smoker from New York City with a cough who goes to a health clinic for any reason.
An anxious 62 year old woman with a headache and muscle aches who calls her doctor.
A healthy 35 year old man presenting for an annual physical, whose blood tests positive for SARS-CoV2 antibodies.
A ailing 88 year old heart failure patient who dies from respiratory failure and whose death certificate reports a possible infection with SARS-CoV2, although no lab tests were performed.
A healthy 28 year old nurse who hasn’t had a cold all year, whose blood tests positive for SARS-CoV2 antibodies.
A 45 year old homeless man with pneumonia who goes to the emergency room but is not tested for SARS-CoV2.
It is important to note, also, that these standards for diagnosis were published on April 5th, so health care providers before then were all diagnosing “cases” differently from each other, based on their own standards. Interestingly, according to the CDC’s reports, the highest number of new cases in one day (43,438) was reported on April 6th. (Don’t worry —since then, the number of new cases per day declined after that peak and has generally leveled off, ranging from 19,138 on May 4th to 37,144 on April 23rd.)
We have heard many times that the majority of those who develop respiratory distress and those who die are elderly or have underlying medical conditions. One thing that should tell us is that maybe it isn’t necessarily the virus that determines the disease, but the patient. Why? Because the virus doesn’t lead to respiratory distress.
For some people infected with SARS-CoV2, when the virus particles get into the lungs, it’s the immune system that causes distress by overreacting with a massive overwhelming response: it floods the lungs with excessive immune-cell troops and weapons, causing damage and fluid accumulation that impede (or, in the worst case scenario, stop) the lung cells from breathing.
Why does this happen in some people and not others? And why almost never in children? There are speculations, but no one knows. It is interesting to note, however, that this same response happens with lab animals who have been given SARS-CoV (the first one) test vaccines and then are later exposed to SARS-CoV. Which is one of the reasons we don’t yet have a vaccine for SARS (or MERS).
SARS-CoV2
SARS-CoV2 stands for “Severe Acute Respiratory Syndrome-COronaVirus 2,” ie, the second coronavirus associated with sudden (= “acute”) respiratory failure. Importantly, only a minority of the people with SARS-CoV2 infections develop any type of illness. Of that minority who actually get sick, a smaller minority develop respiratory distress. And of that number, a still smaller number of people actually die. So far from being the kiss of death, for the vast majority of people, infection with SARS-CoV2 is just like an infection from other coronaviruses: you may get a cold or you may be fine.
So far, with the very limited data available, it seems that a fraction of 1% of people with “COVID-19” actually die. Unfortunately, because of the way the CSTE and the CDC have decided to define cases and deaths — ie, you don’t have to have the virus to be a “case,” and “deaths” don’t have to be caused by the virus — it will be a very long time before we actually know the lethality of this virus.
There are millions of other coronaviruses that are unidentified and several other identified variants without boring alphanumeric names; most of the ones relevant to humans cause the common cold (along with an assortment of other types of viruses). They are called “coronaviruses” because they have linear proteins emanating from their bodies like the corona (or “crown” in Latin) of the sun. Coronaviruses are single stranded RNA viruses surrounded by an envelope.
Influenza-Life Illness (ILI)
For many elderly and seriously ill patients, any infection can be lethal. What may be a simple cold or sinus infection in one person can progress into bronchitis, pneumonia, sepsis, delirium, and even death in others. The microbes that cause most of these illnesses are largely unknown; since we don’t have specific antivirals to treat them, it doesn’t help patients to identify the exact strain of which virus that’s responsible. In fact, there aren’t even tests available for that.
Since there are a vaccine and some therapeutics for influenza, however, we do have tests for flu. And the CDC tracks the numbers for actual, confirmed (to the extent possible) influenza. Everyone else gets grouped under the label “Influenza-Like Illness,” which encompasses a broad array of people. The CDC tracks those numbers as well, since some of these cases may have had influenza but didn’t get tested. Another reason is to detect new epidemics.
If, for example, in a given year, the flu numbers are average but there’s a spike in ILI cases, there is probably a new virus on the scene — possibly a different flu variant, but possibly something totally new — which should be investigated further.
So the question is: if we did not already have a test for SARS-CoV2 available at the start of this pandemic, would there otherwise have been a spike in the ILI deaths/cases that would have raised alarm? Would there have been a reason to go looking for SARS-CoV2? Has there really been a rise in COVID-19 deaths, or are we just reassigning some of them out of the ambiguous “ILI” column and into the more specific “COVID-19” column?
Although it would be great to have an answer for this question, the truth is that I can’t tell. The CDC has used excessively broad definitions which it changed mid-stream, changed death certificate documentation requirements (also mid-stream) for COVID-19 rates (but not flu or ILI), and has even curtailed its usual ILI and flu reporting to better “focus” on COVID-19. This last announcement is head-smackingly ludicrous, as “focus” in this sense unavoidably means loss of perspective (thankfully, at least they are still collecting the data, even if not reporting it).
Whether these decisions were motivated by fear, political pressure, severe short-sightedness, or misguided paternalism is anyone’s guess. It is frankly obvious, however, that accurate and scientifically useful data collection was not the motivation.
Doing the Numbers
Definitions
Definitions that will be useful for this section:
Antigen
Antigens are proteins made by a foreign organism, including viruses like SARS-CoV2, bacteria, and even other humans (ie, infants).
Antigens are stuck on the outside of the virus like a flag on a foreign soldier’s uniform. These usually elicit an immune system response from the host organism (us, in this case). Our cells all wear our flag, so the immune system can easily recognize them as friendly. When the immune system finds foreign flags, special immune cells called “Antigen-Presenting Cells,” take them to supervisor immune cells to see if they match any enemy flags we’ve seen before.
If there’s a match a complex process is triggered to apprehend that bad guy and any of his kind that are lurking around. If there isn’t a match, there is a different process to apprehend them that also involves adding that guy to the existing list of other bad guys and to the alarm system.
Antibody (IgM, IgG)
Antibodies are the chemicals produced by our bodies that attach to specific antigens (flags) on the bad guys.
There are several types of of antibodies; the two types we’ll discuss today IgM and IgG. Typically, IgM is the type made initially and lasts for the first few days to weeks; IgG is the more durable type that is made later. IgG is usually made in low amounts for the rest of the our lives.
If you have anti-SARS-CoV2 IgM in your blood, it means that you were recently infected with the virus — within the past few weeks. If you have anti-SARS-CoV2 IgG in your blood, it means that you were infected with the virus at some point, and if the virus tries to invade you again, your levels of IgG should rise and then fall back down again after the infection. According to the CSTE guidelines, it isn’t clear whether IgM or IgG or both can count as a “positive.”
Antibodies are like LED lights that stick to the bad guy’s uniform and light up all his foreign flags. Antibodies can stick all over a very tiny virion and prevent it from sneaking inside a cell. Once it’s inside a host cell, however, all the antibody can do is alert the other immune cells to the presence of the bad guys so the immune system can take out the infected cell. Antibodies mean the bad guys can’t hide. Having antibodies in your blood (either IgM or IgG), therefore, doesn’t necessarily mean that you are immune to a virus; it simply means that your body can identify it as a bad guy. It’s a good sign, and definitely helpful, but other cells and mechanisms are necessary to get rid of the virus and repair the damage caused in the process.
Another important point is that invaders from the same country usually wear the same flags on their uniforms; therefore, the antibodies that you make to army soldiers from that country may also be helpful fighting naval sailors from that country. In other words, a particular antibody may be able to bind to different but related viruses. Similarly, the “enemy troops” often wear more than just a flag on their uniforms; they usually wear other identifiably enemy insignia (antigens) as well. So several different types of antibodies may bind to one virus, and one antibody may bind to several different types of viruses.
Death Rate
The death rate is the number of people who die because of a particular infection over the total number of people with the infection.
Note that this number will always be higher than the number of people in a population who die, because not everyone in the population will get infected. Also, the greater the number of total cases, the less the death rate will be. Remember, also, that not everyone who gets infected will get sick.
Since those healthy people have little reason to get tested, and since our tests for SARS-CoV2 have limited availability and validity, the healthy people are greatly underrepresented in the case numbers we hear in the media. . Using the numbers we have, therefore, the true death rate is likely to be much lower than the reported death rate (at least for the foreseeable future).
Medical Testing
The most important thing to remember about all medical tests is that they are never 100% accurate. Some tests are quite reliable, while others are little better than a coin toss. We should try to keep that in mind when we hear terms on the news like “laboratory confirmed.”
Currently there are two types of tests being done: genetic tests (from various body fluids) and antibody tests (from studying blood serum, or “serology”).
Genetic Testing
Most of the genetic tests use PCR (Polymerase Chain Reaction) testing to look for viral RNA, and the specific type of PCR used for SARS-CoV2 is called RT RT-PCR, or "RT-PCR" for short (ikr?). Simplified, you take some SARS-CoV2 particles, add some enzymes that chop up the RNA into little bits, then separate out those little bits so that they all line up together. All lined up they make a certain pattern which is used as a reference. You do the same process for patient samples to see if they match the reference pattern.
Although it’s a relatively simple concept, in real life there are a number of steps and reagents that can make things tricky. The current tests we have are all new, approved under the Emergency Use Act by the FDA, so we really don’t know yet how accurate they are. It’s better than having no tests at all, but it’s important to keep in mind that a result — positive or negative — is not a slam dunk answer.
As of this writing, there a handful of labs testing for SARS-CoV2 RNA, looking at a few different genes (well, parts of different genes, anyway), which are thought to be unique to SARS-CoV2. Most of these tests have been designed to find matches to two or three RNA-sections. The CDC test looks for 2 sections of the same gene (and a control).
If we assume the results are accurate, a positive result means you have virus particles in the part of your body that the sample came from — nose, throat, lung, etc. This means a few other things.
You are infected with the virus (as defined earlier).
You could pass on the virus to others.
You may or may not actually feel sick; ie, an infection is not the same as a disease (also defined earlier).
If you are ill, SARS-CoV2 may or may not be the primary reason. For example, if you have a concussion, the virus probably didn’t cause it (although some viruses can pack a punch!).
Whether or not you are ill, congratulations: you now officially count as a confirmed case of COVID-19. If you happen to die in the next few weeks, you will then count as a confirmed death from COVID-19 (even if you die from consequences of that head trauma).
Some other conclusions would also be justified:
Your immune system may respond appropriately and ultimately eradicate the infection, but it hadn’t done so at the time of the test. If/when it does so, you will most likely make antibodies to SARS-CoV2 for the rest of your life.
For a small fraction of people, depending on your age and overall health, your immune system may overreact, filling your lungs up with fluid, leading to respiratory distress and possibly death.
Those are conclusions you could reach if you assume the test results are accurate. So far, however, all of the RNA/genetic tests we have are new and will at some point have to properly validated by objective third parties before we know how to best interpret the results.
Antibody Tests (Seriology)
Antibody tests, on the other hand, are even newer and less clear. They usually utilize a technique called “ELISA” (Enzyme-Linked ImmunoSorbent Assay), sometimes called “EIA” (Enzyme ImmunoAssay). It involves taking some of the viral antigens (the flags and badges on the bad guys’ uniforms) and seeing if your serum contains an antibody to stick to it (that’s the “immunosorbent part;” the “enzyme” part involves a reaction that enables you to actually see the antibodies).
As stated above, a particular virus is usually bound by several different antibodies, and a single antibody may bind to several viruses. This makes antibody testing a bit tricky. Usually, antibody tests focus on a few different antigens (more often, just on certain parts of an antigen) worn by a particular bad guy.
However, a person’s immune system may have made an antibody that binds to a different part of the virus — a different (but equally effective) antibody than the test is looking for. So you may have perfectly fine antibodies to SARS-CoV2, but the test says you are “negative.” This is called a “false negative” result.
You may also have antibodies to a different coronavirus — similar but different from SARS-CoV2 — which shares a “flag” (antigen) with SARS-CoV2. In this case, your test will read “positive” even though you have never been exposed to SARS-CoV2. This is called a “false positive” result.
To be fair, every test has false positives and negatives, which are reflected in the statistical terms “sensitivity” and “specificity.” After reading some of the lab publications about their tests, I am sure they all did their best to eliminate cross-reactivity with other known coronaviruses and to select the most logical antigens, but it's a foolish scientist who believes he knows all there is to know. Most of the tests only use two or three bits of antigens, so there is certainly a lot we could be missing.
Tracking and Reporting
Allow me to state once again that, as of this writing, the CDC is not openly tracking SARS-CoV2.
If they were, they would be using the techniques they have been refining over the past 23 years when they started tracking influenza epi-/pandemics. For flu, they track self-reports in surveys, outpatient visits, hospitalizations, and deaths — for laboratory “confirmed” influenza and for Influenza-Like Illness. The former provides certainty about infection, but misses a lot of disease. The latter includes most cases of disease but lacks information about the exact infection. The combination of both sets of data can give us a better idea of what the real situation might be.
But for COVID-19, we are only tracking the number of cases (confirmed and probable combined, not reported separately) and deaths. And for both metrics, we are including people with known disease and unknown infection status as well as people with known infection status and unknown disease. This is like comparing Granny Smith apples and clementines on one side to red delicious apples and navel oranges on the other. How could we possibly draw any conclusions about all apples and all oranges this way?
Just to underscore the point, consider that the very definition of a confirmed case of the disease COVID-19 is solely based on the lab-detected presence of an infection with SARS-CoV2. This is contradictory from the beginning.
In one single story during my daily global report on coronavirus this morning, the journalist referenced statistics from Australia, Brazil, the U.K., and the U.S., at different times mentioning “cases,” deaths, lab results, SARS-CoV2, and COVID-19 — although each country defines, records, and reports these things differently, not to mention that they are all distinct and separate data sets in their own rights. Are they just not paying attention?
Conclusion
Please, please, I’m begging you to listen critically to what you are being told (by me, too)! Or possibly even what you are being sold.
My clinical experience with thousands of people in crisis situations leads me to believe that we all basically want the same thing — the least amount of risk and the most amount of benefit. We may differ about how to achieve that, but let’s not be falsely divided into opposing camps by statistical chicanery and panic politics.
Whether we want masks or no masks, to stay home or go back to work, social distancing or contact sports, let’s recognize at least that we are all on the same side and try to discuss it openly without just arguing ourselves further away from consensus. This isn't an election, after all.
Next time, before we return to our Superpower Series, I’ll extend this discussion of COVID-19 specific issues into questions that are looming in our near future, hoping to provide some lesser-known information that is important for us to think about as we try to form our own individual opinions. This will include the topics of: herd immunity, the false dichotomy between the individual and the collective, the so-called second wave, and maybe even vaccination (!).
Until then, stay thinking, my friends.
